We will investigate clinical, biochemical and genetic aspects of hypertriglyceridemia. Our focus is on the pathogenesis and inheritance of hypertriglyceridemia and on the role of lipoprotein lipase in the metabolism of triglyceride-rich lipoproteins in man. We have undertaken these studies in selected families since it is more likely that the results obtained will reflect the effects of discrete biochemical defects. The investigation will define attributes of a subset of individuals potentially at risk for coronary heart disease. The project is designed to test the hypothesis that partial lipoprotein lipase deficiency exists in selected pedigrees and contributes to the pathogenesis of acquired hyperlipoproteinemia. Lipoprotein lipase activity will be measured both in post-heparin plasma and adipose tissue by selective methods. We will also screen kindred for deficiency of LPL-activating apolipoprotein peptides. Provocative testing will be used to determine whether genetic predisposition to hypertriglyceridemia can be unmasked in individuals thought to be heterozygous for an LPL deficient/defective gene. Data will be examined to determine whether phenotypically distinct subpopulations are present among first-degree relatives at risk for hypertriglyceridemia. Segregation analysis of simple Mendelian inheritance will be performed when distinct subpopulations are identified.